Publications by authors named "Ju-Wei Hsu"

91 Publications

Associations between increased circulating endothelial progenitor cell levels and anxiety/depressive severity, cognitive deficit and function disability among patients with major depressive disorder.

Sci Rep 2021 Sep 14;11(1):18221. Epub 2021 Sep 14.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.

The association of major depressive disorder (MDD) with cardiovascular diseases (CVDs) through endothelial dysfunction is bidirectional. Circulating endothelial progenitor cells (cEPCs), essential for endothelial repair and function, are associated with risks of various CVDs. Here, the relationship of cEPC counts with MDD and the related clinical presentations were investigated in 50 patients with MDD and 46 healthy controls. In patients with MDD, a battery of clinical domains was analysed: depressed mood with Hamilton Depression Rating Scale (HAMD) and Montgomery-Åsberg Depression Rating Scale (MADRS), anxiety with Hamilton Anxiety Rating Scale (HAMA), cognitive dysfunction and deficit with Digit Symbol Substitution Test (DSST) and Perceived Deficits Questionnaire-Depression (PDQ-D), somatic symptoms with Depressive and Somatic Symptom Scale (DSSS), quality of life with 12-Item Short Form Health Survey (SF-12) and functional disability with Sheehan Disability Scale (SDS). Immature and mature cEPC counts were measured through flow cytometry. Increased mature and immature cEPC counts were significantly associated with higher anxiety after controlling the confounding effect of systolic blood pressure, and potentially associated with more severe depressive symptoms, worse cognitive performance and increased cognitive deficit, higher social disability, and worse mental health outcomes. Thus, cEPCs might have pleiotropic effects on MDD-associated symptoms and psychosocial outcomes.
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http://dx.doi.org/10.1038/s41598-021-97853-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440504PMC
September 2021

Associations between increased circulating endothelial progenitor cell levels and anxiety/depressive severity, cognitive deficit and function disability among patients with major depressive disorder.

Sci Rep 2021 Sep 14;11(1):18221. Epub 2021 Sep 14.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.

The association of major depressive disorder (MDD) with cardiovascular diseases (CVDs) through endothelial dysfunction is bidirectional. Circulating endothelial progenitor cells (cEPCs), essential for endothelial repair and function, are associated with risks of various CVDs. Here, the relationship of cEPC counts with MDD and the related clinical presentations were investigated in 50 patients with MDD and 46 healthy controls. In patients with MDD, a battery of clinical domains was analysed: depressed mood with Hamilton Depression Rating Scale (HAMD) and Montgomery-Åsberg Depression Rating Scale (MADRS), anxiety with Hamilton Anxiety Rating Scale (HAMA), cognitive dysfunction and deficit with Digit Symbol Substitution Test (DSST) and Perceived Deficits Questionnaire-Depression (PDQ-D), somatic symptoms with Depressive and Somatic Symptom Scale (DSSS), quality of life with 12-Item Short Form Health Survey (SF-12) and functional disability with Sheehan Disability Scale (SDS). Immature and mature cEPC counts were measured through flow cytometry. Increased mature and immature cEPC counts were significantly associated with higher anxiety after controlling the confounding effect of systolic blood pressure, and potentially associated with more severe depressive symptoms, worse cognitive performance and increased cognitive deficit, higher social disability, and worse mental health outcomes. Thus, cEPCs might have pleiotropic effects on MDD-associated symptoms and psychosocial outcomes.
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http://dx.doi.org/10.1038/s41598-021-97853-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440504PMC
September 2021

Risk of attention deficit hyperactivity and autism spectrum disorders among the children of parents with autoimmune diseases: a nationwide birth cohort study.

Eur Child Adolesc Psychiatry 2021 Aug 13. Epub 2021 Aug 13.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.

Studies have suggested that maternal autoimmune diseases are associated with an increased risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, research on the association of paternal autoimmune diseases with ADHD and ASD risk has remained inconclusive. Using the Taiwan National Health Insurance Research Database, we selected 708,517 family triads (father-mother-child) between 2001 and 2008 and followed them until the end of 2011. Parental autoimmune diseases as well as ADHD and ASD in children were identified during the study period. Increased ADHD risk in children in terms of hazard ratios (HRs) and 95% confidence intervals (CIs) was associated with prenatal exposure to paternal autoimmune diseases, including Sjögren's syndrome (HR: 8.41, 95% CI: 2.72-26.05), psoriasis (HR: 1.95, 95% CI: 1.05-3.63), and ankylosing spondylitis (HR: 2.02, 95% CI: 1.29-2.15), as well as maternal autoimmune diseases, such as systemic lupus erythematosus (HR: 1.53, 95% CI: 1.09-2.15), type 1 diabetes mellitus (HR: 1.55, 95% CI: 1.02-2.36), inflammatory bowel disease (HR: 2.37, 95% CI: 1.59-3.52), psoriasis (HR: 1.70, 95% CI: 1.00-2.87), and ankylosing spondylitis (HR: 2.07, 95% CI: 1.11-3.86). However, ASD was only associated with paternal inflammatory bowel disease (HR: 3.08, 95% CI: 1.15-8.28) and ankylosing spondylitis (HR: 2.65, 95% CI: 1.10-6.39). Both paternal and maternal autoimmune diseases were associated with increased likelihood of ADHD in children. However, only paternal autoimmune diseases were related to offspring ASD risk. The precise pathomechanism underlying the correlation between parental autoimmunity and child neurodevelopment requires further investigation.
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http://dx.doi.org/10.1007/s00787-021-01860-0DOI Listing
August 2021

Postpartum Depression and Psychosis and Subsequent Severe Mental Illnesses in Mothers and Neurodevelopmental Disorders in Children: A Nationwide Study.

J Clin Psychiatry 2021 Jul 27;82(4). Epub 2021 Jul 27.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

The association between postpartum depression and postpartum psychosis and subsequent maternal and offspring mental disorders in Western countries has been established; however, whether the relationship can be generalized to the Asian population is unknown.

Using the Taiwan National Health Insurance Research Database, this study enrolled 933,745 mother-infant pairs who delivered their first child and had no history of severe mental illness before childbirth from 2001 to 2010. Postpartum depression and postpartum psychosis were assessed in 3 periods between childbirth and 3, 6, or 12 months after childbirth. Subsequent maternal schizophrenia ( code: 295), bipolar disorder ( code: 296 except 296.2x, 296.3x, 296.9x, and 296.82), and depressive disorder ( codes: 296.2x, 296.3x, 300.4, and 311) and offspring autism spectrum disorder (ASD; code: 299) and attention-deficit/hyperactivity disorder (ADHD; code: 314) were identified during the follow-up period to the end of 2011.

Both postpartum depression and postpartum psychosis were found to be related to increased risks of schizophrenia, bipolar disorder, and depressive disorder in mothers, with hazard ratios (HRs) ranging between 8.80 (95% CI, 7.95-9.74) and 63.96 (95% CI, 50.39-81.18). Children exposed to maternal postpartum depression and psychosis were more likely to develop ADHD. Only postpartum depression was related to the likelihood of offspring ASD.

Per these findings, we clinicians and health care providers should closely monitor the mental health condition of postpartum women and their children.
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http://dx.doi.org/10.4088/JCP.20m13735DOI Listing
July 2021

The Risk of Alzheimer's Disease After Acute Appendicitis With or Without Appendectomy.

J Am Med Dir Assoc 2021 Jul 13. Epub 2021 Jul 13.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan. Electronic address:

Objective: Previous epidemiologic studies have suggested an association between appendectomy and Parkinson's disease. The aim of the current study was to examine the risk of Alzheimer's disease (AD) and other types of dementia following appendicitis or appendectomy for appendicitis.

Design: Population-based cohort study.

Setting And Participants: We used claims data from the Taiwan National Health Insurance Research Database. Participants aged ≥45 years with acute appendicitis or who received appendectomy for appendicitis were enrolled and followed up for more than 15 years. Cases and controls underwent 1:1 matching by age, sex, index date, and dementia-related comorbidities.

Methods: The primary outcome was AD, and secondary outcomes included other dementia types. Adjusted hazard ratios (aHRs) were calculated, and a competing risk regression model was created. The E value for causality of evidence was calculated.

Results: Patients developing appendicitis (0.6% vs 0.1%, P = .005) and those receiving appendectomy for appendicitis (0.4% vs 0.1%, P = .003) had higher incidences of AD than the controls during the follow-up period. A Cox regression analysis with adjustment for potential confounders showed that patients with appendicitis [aHR 6.68, 95% confidence interval (CI) 1.84-24.48] and those receiving appendectomy for appendicitis (aHR 5.01, 95% CI 1.33-18.85) were more likely to develop AD than the controls. These 2 groups also had higher risks for unspecified dementia and all types of dementia but not for vascular dementia than the controls. The age at dementia diagnosis was 88.51 years in the controls; however, among people who developed dementia following appendicitis, the mean age at diagnosis was 70.18 years, and dementia occurred 5.84 years after appendicitis. The competing risk regression models and the E values support the study findings.

Conclusions And Implications: After recovery from appendicitis, these patients should be followed up for signs of AD.
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http://dx.doi.org/10.1016/j.jamda.2021.06.013DOI Listing
July 2021

Effect of relative age on childhood mental health: A cohort of 9,548,393 children and adolescents.

Acta Psychiatr Scand 2021 08 1;144(2):168-177. Epub 2021 Jun 1.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The effect of relative age on the diagnoses of attention deficit hyperactivity disorder (ADHD), disruptive behavior disorder (DD), anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications remains unclear.

Aim: To clarify the impact of relative age in a school year with the diagnoses of ADHD, DD, anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications.

Methods: The annual cutoff birthdate for entry to school in Taiwan is August 31. The Taiwan National Health Insurance Research Database was used to enroll 9,548,393 children and adolescents aged 3-17 years during the study period (September 1, 2001, to August 31, 2011). The Poisson regression model was performed to examine the likelihood of receiving diagnoses of ADHD, DD, anxiety disorder, and depressive disorder, as well as the prescription of ADHD and antidepressant medications among children born in August (the youngest) and September (the oldest).

Results: Both boys and girls born in August had a higher risk of being diagnosed as having ADHD (odds ratio [OR] = boys: 1.65, girls: 1.80), DD (1.29, 1.45), anxiety disorder (1.49, 1.33), and depressive disorder (1.10, 1.10). Furthermore, children born in August were more likely to be prescribed ADHD medication (1.71, 1.72) and antidepressants (1.18, 1.09) compared with those born in September.

Discussion: Relative age, as an indicator of neurocognitive maturity, is a critical factor for the likelihood of being diagnosed as having ADHD, DD, anxiety disorder, and depressive disorder among children and adolescents.
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http://dx.doi.org/10.1111/acps.13327DOI Listing
August 2021

Effect of relative age on diagnosis of autism spectrum disorder in children: a nationwide study in Taiwan.

Eur Child Adolesc Psychiatry 2021 May 8. Epub 2021 May 8.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, Taipei, 11217, Taiwan.

Background: The annual cut-off birthdate for entry into school in Taiwan is August 31. Thus, children and adolescents born in August are typically the youngest in their grades. The potential effect of relative age on the diagnosis of autism spectrum disorder (ASD) remains uncertain.

Methods: A total of 9,548,393 individuals aged 3-17 years during the study period (from September 1, 2001, to August 31, 2011) identified from the Taiwan National Health Insurance Research Database were enrolled into our study. Logistic regression analysis was used to examine the likelihood of receiving ASD diagnosis for those who were born in August (the youngest) compared with those who were born in September (the oldest).

Results: Both boys and girls born in August had a higher likelihood of being diagnosed with ASD (odds ratio [OR]: 1.24, 95% confidence interval [CI]: 1.16-1.32; OR: 1.23, 95% CI 1.06-1.42) than did those born in September. Sensitivity analysis conducted over different periods revealed consistent findings.

Discussion: Relative age, as an indicator of neurocognitive maturity, is a crucial contributor to the risk of being diagnosed with ASD among children and adolescents. Our findings highlight the importance of considering the age of a child within a grade when diagnosing ASD.
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http://dx.doi.org/10.1007/s00787-021-01791-wDOI Listing
May 2021

Developmental and mental health risks among siblings of patients with autism spectrum disorder: a nationwide study.

Eur Child Adolesc Psychiatry 2021 Apr 18. Epub 2021 Apr 18.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.

Studies have suggested that unaffected siblings of patients with autism spectrum disorder (ASD) have some other neurodevelopmental abnormalities. However, the risks of mental and developmental disorders have rarely been investigated among unaffected siblings. Using Taiwan's National Health Insurance Research Database, 1304 unaffected siblings born between 1980 and 2010 with ASD probands and 13,040 age-/sex-/family structure-matched controls were included in our study and followed up from 1996 or birth to the end of 2011. Developmental delay, language delay, developmental coordination disorder, attention-deficit hyperactivity disorder (ADHD), anxiety disorders, disruptive behavior disorders, unipolar disorder, and bipolar disorder were identified during the follow-up period. Unaffected siblings were more likely to develop any developmental delay, developmental speech or language disorder, developmental coordination disorder, intelligence disability, ADHD, anxiety disorders, unipolar depression, and disruptive behavior disorders compared with the control group. Brothers of patients with ASD had a higher risk of neurodevelopmental abnormalities, ADHD, anxiety disorders, and disruptive behavior disorders; sisters were prone to having neurodevelopmental abnormalities, ADHD, anxiety disorders, unipolar depression, and disruptive behavior disorders. Unaffected siblings of patients with ASD were prone to developing any developmental or mental disorder later in life. Clinicians and public health officials should pay more attention to the developmental condition and mental health of unaffected siblings of patients with ASD.
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http://dx.doi.org/10.1007/s00787-021-01784-9DOI Listing
April 2021

The Risk of Epilepsy after Long-term Proton Pump Inhibitor Therapy.

Seizure 2021 Apr 11;87:88-93. Epub 2021 Mar 11.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address:

Background: Prescription-event monitoring studies have reported incident epilepsy or seizures in proton pump inhibitor (PPI) recipients. We examined the risk of epilepsy after prolonged PPI exposure and determine what age group was at higher risk of epilepsy.

Methods: We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000). PPI users with subsequent epilepsy were selected as the case cohort. Controls were PPI users without subsequent epilepsy, matched for age, sex, PPI use indication, enrollment time, end point time, follow-up period, overall systemic health, and comorbidities. The total dose of PPI was defined as the cumulative defined daily dose (cDDD). Prolonged PPI use was defined as a cDDD > 365. A logistic regression analysis was performed. Population attributable risk was calculated.

Results: Epilepsy occurred 4.13 years after the initiation of PPI use. PPI users with the highest risk of incident epilepsy received a cDDD > 365 [odds ratio = 1.63, 95% confidence interval = 1.37-1.95], followed by 121-365 cDDD (1.33, 1.18-1.51) and 31-120 cDDD (1.15, 1.02-1.29), compared to those receiving a cDDD ≤ 30, after adjusting for potential confounders. Prolonged PPI use increased the risk of epilepsy in all age groups, and the risk was highest for those older than 80 years (3.11, 1.67-5.79). The population attributable risk was 12.2% (> 365 cDDD vs ≤ 30 cDDD).

Discussion: Prolonged PPI therapy was associated with an increased risk of epilepsy, particularly in the elderly population.
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http://dx.doi.org/10.1016/j.seizure.2021.03.008DOI Listing
April 2021

Using classification and regression tree modeling to investigate appetite hormones and proinflammatory cytokines as biomarkers to differentiate bipolar I depression from major depressive disorder.

CNS Spectr 2021 Feb 10:1-7. Epub 2021 Feb 10.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Altered immunity and metabolic profiles have been compared between bipolar depression (BD) and major depressive disorder (MDD). This study aimed at developing a composite predictor of appetite hormones and proinflammatory cytokines to differentiate BD from MDD.

Methods: This cross-sectional study enrolled patients with BD and those with MDD aged 20 to 59 years and displaying depressive episodes. Clinical characteristics (age, sex, body mass index, and depression severity), cytokines (C-reactive protein, interleukin [IL]-2, IL-6, tumor necrosis factor [TNF]-α, P-selectin, and monocyte chemoattractant protein), and appetite hormones (leptin, adiponectin, ghrelin, and insulin) were assessed as potential predictors using a classification and regression tree (CRT) model for differentiating BD from MDD.

Results: The predicted probability of a composite predictor of ghrelin and TNF-α was significantly greater (for BD: area under curve = 0.877; for MDD: area under curve = 0.914) than that of any one marker (all P > .05) to distinguish BD from MDD. The most powerful predictors for diagnosing BD were high ghrelin and TNF-α levels, whereas those for MDD were low ghrelin and TNF-α levels.

Conclusion: A composite predictor of ghrelin and TNF-α driven by CRT could assist in the differential diagnosis of BD from MDD with high specificity. Further clinical studies are warranted to validate our results and to explore underlying mechanisms.
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http://dx.doi.org/10.1017/S109285292100016XDOI Listing
February 2021

Factors Affecting Delayed Initiation and Continuation of Medication Use for Attention-Deficit/Hyperactivity Disorder: A Nationwide Study.

J Child Adolesc Psychopharmacol 2021 04 18;31(3):197-204. Epub 2021 Jan 18.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

This study evaluated the predictors for delayed initiation and continuation of ADHD medication use in children and adolescents with ADHD in Taiwan. This longitudinal cohort study enrolled 188,061 children and adolescents with ADHD between 2001 and 2011. Delayed initiation of ADHD medications was defined as the interval >365 days between diagnosis and first prescription, and continuation of ADHD medications was defined as ≥365 defined daily doses of ADHD medications. Of the included patients, 39.2% were never treated with ADHD medications. Delayed initiation and continuation of ADHD medication use were found in 11.9% and 19.9% of the ever-treated patients, respectively. Younger age at ADHD diagnosis, male sex, older mother's age at child's ADHD diagnosis, and higher family income were associated with more delayed initiation but were also associated with more continuation of ADHD medication use. The initiation and continuation of ADHD medication use might be underlined by different mechanisms and warrant different strategies.
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http://dx.doi.org/10.1089/cap.2020.0136DOI Listing
April 2021

Identification of common neural substrates with connectomic abnormalities in four major psychiatric disorders: A connectome-wide association study.

Eur Psychiatry 2020 12 3;64(1):e8. Epub 2020 Dec 3.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei112, Taiwan.

Background: Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).

Methods: This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.

Results: The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.

Conclusions: These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.
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http://dx.doi.org/10.1192/j.eurpsy.2020.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057470PMC
December 2020

Proinflammatory Cytokine Dysregulation and Cognitive Dysfunction Among Patients with Remitted Bipolar I and II Disorders.

J Affect Disord 2021 02 16;281:738-743. Epub 2020 Nov 16.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital. Electronic address:

Background: Euthymic patients with bipolar disorder reportedly demonstrated increased levels of proinflammatory cytokines and cognitive function deficits. Because uncertain differences exist in cognitive function and proinflammatory cytokines between remitted bipolar I (BD1) and bipolar II (BD2) disorders, we performed this study to further investigate these differences.

Method: We enrolled 58 patients with remitted BD1 and 27 with remitted BD2, and matched them for age and sex with 51 controls. Proinflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), C-reactive protein, and soluble tumor necrosis factor receptor 1 (sTNFR1) were measured, and performance in the Word List Memory Task (WLMT) and Wisconsin Card Sorting Task (WCST) was assessed.

Results: Significantly elevated levels of sTNFR1 were observed among patients with BD1 (p < .001) and BD2 (p = .038) compared with the controls; however, they did not differ between patients with BD1 and BD2 (p =.130). Working memory deficit measured by the WLMT was significantly greater in patients with BD1 (p < .001) and BD2 (p < .05) compared with controls, but did not differ between patients with BD1 and BD2 (p > 0.1). Furthermore, sTNFR1 levels were negatively correlated with cognitive function measured using the WLMT and WCST (all p < .05).

Discussion: Our results showed that euthymic patients with BD1 and BD2 showed similar levels of sTNFR1 and cognitive function (especially working memory) impairments. Further investigation is required to explore whether a common pathophysiology may contribute to the shared inflammatory and cognitive alterations between BD1 and BD2.
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http://dx.doi.org/10.1016/j.jad.2020.11.079DOI Listing
February 2021

Bidirectional association between migraine and depression among probands and unaffected siblings: A nationwide population-based study.

J Affect Disord 2021 01 29;279:687-691. Epub 2020 Oct 29.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Evidence suggests a bidirectional association between migraine and depression in individuals and in twins. However, whether a bidirectional association between migraine and depression also occurs among siblings (probands and unaffected nontwin siblings) remains unknown.

Methods: Using the Taiwan National Health Insurance Research Database, we examined the data of 1504 probands with migraine, 1595 unaffected siblings, and 6380 nonmigrainous controls born before 2000 to identify new-onset depression for the period between 1996 and 2011. Conversely, 31824 probands with depression, 34325 unaffected siblings, and 137300 nondepressive controls were examined for the identification of new-onset migraine.

Results: Logistic regression analyses demonstrated that compared with the controls, patients with migraine (odds ratio [OR]: 4.09; 95% confidence interval [CI]: 3.75-4.46) and unaffected siblings (OR: 1.40; 95% CI: 1.24-1.58) were more likely to develop depression during the follow-up period. Moreover, patients with depression and unaffected siblings had a 4.13-fold (95% CI: 3.18-5.36) and 1.45-fold (95% CI: 1.03-2.05) increased risk of migraine.

Discussion: The bidirectional association between migraine and depression among probands and unaffected siblings suggests a familial coaggregation of these two conditions. Additional studies are required to investigate the genetic and environmental etiologies for this coaggregation.
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http://dx.doi.org/10.1016/j.jad.2020.10.056DOI Listing
January 2021

Network-Specific Corticothalamic Dysconnection in Attention-Deficit Hyperactivity Disorder.

J Dev Behav Pediatr 2021 Feb-Mar 01;42(2):122-127

Department of Psychiatry, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.

Background: Functional connectivity (FC) is believed to be abnormal in attention-deficit hyperactivity disorder (ADHD). Most studies have focused on frontostriatal systems, and the role of the thalamic network in ADHD remains unclear. The current study used FC magnetic resonance imaging (fcMRI) to explore corticothalamic network properties and correlated network dysconnection with ADHD symptom severity.

Methods: Eighteen adolescents with ADHD and 16 healthy controls aged 12 to 17 years underwent resting functional MRI scans, clinical evaluations, and 2 parent rating scales, namely the Swanson, Nolan, and Pelham IV scale and the Child Behavior Checklist. Six a priori cortical regions of interest were used to derive 6 networks: the dorsal default mode network, frontoparietal network, cingulo-opercular network (CON), primary sensorimotor network (SM1), primary auditory network, and primary visual network (V1). The corticothalamic connectivity for each network was calculated for each participant and then compared between the groups. We also compared the 2 scales with the network connectivity.

Results: The corticothalamic connectivity within the CON was significantly reduced (p < 0.05) among adolescents with ADHD compared with the controls. The corticothalamic dysconnection within the CON, SM1, and V1 networks negatively correlated with ADHD symptom severity.

Conclusion: This network analysis indicates that corticothalamic dysconnection in ADHD involves the CON, SM1, and V1 networks and relates to symptom severity. The findings provide evidence of dysfunctional thalamus-related networks in ADHD.
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http://dx.doi.org/10.1097/DBP.0000000000000875DOI Listing
February 2020

Cardiometabolic disease risk among siblings of patients with major depressive disorder.

J Dev Orig Health Dis 2021 Jun 14;12(3):530-535. Epub 2020 Sep 14.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.
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http://dx.doi.org/10.1017/S2040174420000860DOI Listing
June 2021

Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study.

Psychol Med 2020 Sep 11:1-11. Epub 2020 Sep 11.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.

Methods: This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).

Results: FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50-19.67), ADHD 3.94 (CI 3.72-4.17), schizophrenia 3.05 (CI 2.74-3.40), BD 2.22 (CI 1.98-2.48) and MDD 1.88 (CI 1.76-2.00). Higher RRs of schizophrenia (4.47, CI 3.95-5.06) and ASD (18.54, CI 16.18-21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.

Conclusions: The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.
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http://dx.doi.org/10.1017/S0033291720003207DOI Listing
September 2020

Role of appetite hormone dysregulation in the cognitive function among patients with bipolar disorder and major depressive disorder.

World J Biol Psychiatry 2021 07 23;22(6):428-434. Epub 2020 Sep 23.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Objectives: The association of appetite hormones with cognitive function in patients with affective disorders remains unknown.

Methods: All total, 58 adult patients with bipolar I disorder, 36 with bipolar II disorder, 40 with major depressive disorder were enrolled and age and sex-matched with 40 controls. The levels of appetite hormones leptin, ghrelin, insulin and adiponectin were assessed. Wisconsin Card Sorting Test was used to assess executive function.

Results: A general linear model, adjusted for demographic data and clinical symptoms, demonstrated the ghrelin levels were higher in patients with bipolar I or II disorder than in those with major depressive disorder and controls ( < 0.001). We also identified a positive correlation of ghrelin level and executive function among patients with bipolar I ( = 0.033) and II ( = 0.027) disorders, but not among those with major depressive disorder and controls.

Conclusions: Patients with bipolar I or II disorder were more likely to have high levels of ghrelin than patients with major depressive disorder and controls, which may have a positive correlation on the cognitive function of patients with bipolar I or II disorder.
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http://dx.doi.org/10.1080/15622975.2020.1819566DOI Listing
July 2021

Association of parental depression with offspring attention deficit hyperactivity disorder and autism spectrum disorder: A nationwide birth cohort study.

J Affect Disord 2020 12 19;277:109-114. Epub 2020 Jul 19.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217 Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan. Electronic address:

Background: Studies have indicated that parental depression was slightly related to the increased risk of offspring attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, the association between exposure to parental depression at different neurodevelopmental stages (i.e., perinatal or postnatal period) and subsequent ADHD and ASD development remained uncertain.

Method: 708,515 children born between 2001 and 2008 were screened for ADHD and ASD based on ICD-9-CM codes of 314 and 299 given by psychiatrists from their birth to the end of 2011. Paternal and maternal depression was separately assessed during five periods, namely those before pregnancy (pre-pregnancy), during pregnancy (perinatal), and <1, 1-3, and >3 years after childbirth (postnatal). Cox regression analyses were performed.

Results: Both paternal and maternal depression occurring in the pre-pregnancy, perinatal and postnatal periods were significantly associated with subsequent ADHD and ASD in the offspring, with hazard ratios between 1.42 (95% confidence interval [CI]: 1.35-1.49) and 2.25 (2.09-2.41). The chronicity and additive effect of paternal and maternal depression were related to increased risks of offspring ADHD and ASD. The effects of maternal depression were stronger than the effects of paternal depression for offspring ADHD (HR: 1.35, 95% CI: 1.27-1.45) and ASD (HR: 1.23, 95% CI: 1.05-1.46) risks.

Conclusion: Both paternal depression and maternal depression in the pre-pregnancy, perinatal and postnatal periods increases offspring ADHD and ASD risks, and these risks increase further with increases in the duration of parental depression and with the additive effect of parental and maternal depression.
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http://dx.doi.org/10.1016/j.jad.2020.07.059DOI Listing
December 2020

Sexually transmitted infections among adolescents with conduct disorder: a nationwide longitudinal study.

Eur Child Adolesc Psychiatry 2021 Aug 28;30(8):1187-1193. Epub 2020 Jul 28.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, Taipei, 11217, Taiwan, ROC.

Studies have demonstrated that conduct disorder is related to risky sexual behaviors, the dominant risk factor for contracting a sexually transmitted infection (STI). However, the association between conduct disorder and STIs remains unclear. Using the Taiwan National Health Insurance Research Database, 5733 adolescents with conduct disorder and 22,932 age- and sex-matched controls without conduct disorder were enrolled from 2001 to 2009 and were subject to follow-up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was performed to examine the likelihood of subsequently contracting an STI for patients and controls. Patients with conduct disorder were more likely than controls to develop any STI (HR 3.95, 95% CI 2.97-5.26) after adjusting for demographic data, psychiatric comorbidities, and use of medications. Long-term use of second-generation antipsychotics (SGAs) was related to a reduced risk (HR 0.36, 95% CI 0.14-0.91) of developing an STI among patients with conduct disorder. Adolescents with conduct disorder had an increased risk of developing any STI later in life compared with those without conduct disorder. Long-term use of SGAs was associated with a lower risk of subsequent STI.
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http://dx.doi.org/10.1007/s00787-020-01605-5DOI Listing
August 2021

Increased Proinflammatory Cytokines, Executive Dysfunction, and Reduced Gray Matter Volumes In First-Episode Bipolar Disorder and Major Depressive Disorder.

J Affect Disord 2020 09 3;274:825-831. Epub 2020 Jun 3.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Backgrounds: The association between systemic inflammation, executive dysfunction, and gray matter (GM) volume difference in first-episode affective disorders, including bipolar and major depressive disorders, is unclear.

Methods: Twenty-two patients with first-episode bipolar disorder, 22 age- and sex-matched patients with first-episode major depressive disorder, and 22 matched controls were enrolled in our study; all patients underwent comprehensive assessments, including clinical assessment, executive function examination (Wisconsin card sorting test [WCST]), proinflammatory cytokine receptors (soluble interleukin-6 receptor and tumor necrosis factor-α receptor 1 [TNFR1]), and brain magnetic resonance imaging. Voxel-based morphometry was performed to analyze the GM volume difference between bipolar and major depressive disorders.

Results: Patients with bipolar disorder were more likely to exhibit higher levels of TNFR1 (P = .038), more number of deficits in WCST (P < .05), and smaller GM volume in the middle frontal cortex (uncorrected voxel level P < .001) compared with those with major depressive disorder and healthy controls. Positive associations were observed between the middle frontal cortex volume, executive function, and the TNFR1 level.

Discussion: GM volume reduction in the middle frontal cortex, a greater level of systemic inflammation, and executive dysfunction were observed in first-episode affective disorders, especially bipolar disorder. A positive correlation between middle frontal cortex volume, executive function, and the TNFR1 level may indicate a divergent effect of brain and systemic inflammation functioning in the early phase (first episode) of affective disorder.
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http://dx.doi.org/10.1016/j.jad.2020.05.158DOI Listing
September 2020

Role of obesity in systemic low-grade inflammation and cognitive function in patients with bipolar I disorder or major depressive disorder.

CNS Spectr 2020 Jun 29:1-7. Epub 2020 Jun 29.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background.: Studies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear.

Methods.: Overall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines-including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)-were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task.

Results.: Patients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level.

Conclusions.: Our findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.
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http://dx.doi.org/10.1017/S1092852920001534DOI Listing
June 2020

The Risk of Sexually Transmitted Infections Following First-Episode Schizophrenia Among Adolescents and Young Adults: A Cohort Study of 220 545 Subjects.

Schizophr Bull 2020 07;46(4):795-803

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Young people are disproportionately affected by sexually transmitted infections (STIs). The risk of STIs in young people following first-episode schizophrenia is unknown. This study using Taiwan's National Health Insurance Research Database enrolled 44 109 adolescents and young adults with first-episode schizophrenia and 176 436 age- and sex-matched controls without schizophrenia from 2001 through 2009 and followed to the end of 2011. New-onset STIs were identified. Survival analysis was performed. Cox regression analysis was used to examine the effects of comorbid substance use disorder (SUD), schizophrenia medications, and schizophrenia severity. The E value for causality of evidence was calculated. We found that young people had a higher risk of STIs following first-episode schizophrenia compared with controls without schizophrenia (hazard ratio [HR] = 2.35, 95% CI = 2.08-2.64); these STIs included human immunodeficiency virus (HIV) (3.70, 2.60-5.28) and syphilis (5.35, 3.96-7.23). They also showed a disproportionate distribution of STIs, with an increased proportion of syphilis (20.4% vs 8.2%) and HIV (9.1% vs 6.0%). When presenting with SUD, the risks of HIV (11.00, 7.02-17.25) and syphilis (9.11, 6.16-13.47) were further increased. The severe schizophrenia group had an extremely high risk of syphilis (41.26, 27.69-61.47) and HIV (7.50, 3.85-14.62). Schizophrenia medications may provide beneficial effects against contracting STIs (0.77, 0.68-0.89). We concluded that following first-episode schizophrenia, young patients are at higher risk of STIs, particularly HIV and syphilis. The risk further increased when subjects presented with SUD or severe schizophrenia. Importantly, antipsychotic treatment may lower the risk of STIs.
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http://dx.doi.org/10.1093/schbul/sbz126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344918PMC
July 2020

A comparison study of metabolic profiles, immunity, and brain gray matter volumes between patients with bipolar disorder and depressive disorder.

J Neuroinflammation 2020 Jan 30;17(1):42. Epub 2020 Jan 30.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.

Background: Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD.

Methods: In this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed.

Results: Compared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels.

Conclusions: Our results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines.
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http://dx.doi.org/10.1186/s12974-020-1724-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990475PMC
January 2020

Functional connectivity of specific brain networks related to social and communication dysfunction in adolescents with attention-deficit hyperactivity disorder.

Psychiatry Res 2020 02 13;284:112785. Epub 2020 Jan 13.

Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan; Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Adolescents with attention-deficit hyperactivity disorder (ADHD) may have impaired social cognition and communication. However, the functioning of the brain networks involved in the social cognition and communication impairment in ADHD patients remains unclear.

Methods: In total, 18 adolescents with ADHD and 16 age- and sex-matched typically developing adolescents (controls)-all of whom underwent a brain magnetic resonance imaging examination-were enrolled. Their parents filled out Swanson, Nolan, and Pelham IV (SNAP-IV) and Social Responsiveness Scale (SRS) questionnaires. Functional connectivity analyses based on the default mode network, frontoparietal network, and cinguloopercular network were performed.

Results: Compared with controls, adolescents with ADHD exhibited higher total and subscale scores on SNAP-IV and SRS. Higher SNAP-IV and SRS scores were associated with higher functional connectivity between the default mode network (ventromedial prefrontal cortex) and cinguloopercular network (anterior insula) and between the FPN (dorsolateral and prefrontal cortex) and cinguloopercular network, but with lower functional connectivity between the default mode network (posterior cingulate cortex) and frontoparietal network (inferior parietal lobule) and between the default mode network (precuneus) and cinguloopercular network (temporoparietal junction).

Discussion: Social cognition and communication impairment and ADHD may commonly share the aberrant functional connectivity in the default mode network, frontoparietal network, and cinguloopercular network.
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http://dx.doi.org/10.1016/j.psychres.2020.112785DOI Listing
February 2020

Early Pregnancy Risk Among Adolescents With ADHD: A Nationwide Longitudinal Study.

J Atten Disord 2021 07 23;25(9):1199-1206. Epub 2020 Jan 23.

Taipei Veterans General Hospital, Taipei.

ADHD potentially leads to risky sexual behaviors, and is considered a major risk factor for early pregnancy (EP). However, the association between ADHD and subsequent EP remains unknown. Seven thousand five hundred five adolescents with ADHD and 30,020 age- and sex-matched individuals without ADHD were enrolled from 2001 to 2009 and were followed until the end of 2011. Adolescents who developed any pregnancy (at age ≤30 years) or EP (at age <20 years) during the follow-up period were identified. Adolescents with ADHD were found to be prone to pregnancy (hazard ratio [HR] = 1.27) and EP (HR = 2.30) compared with those without ADHD. Long-term ADHD medication use was related to a lower risk of subsequent any pregnancy (HR = 0.72) and EP (HR = 0.69). Adolescents with ADHD had an increased risk of any pregnancy and EP compared with their non-ADHD counterparts. Long-term ADHD medication use was associated with a lower subsequent EP risk.
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http://dx.doi.org/10.1177/1087054719900232DOI Listing
July 2021

A child with moyamoya disease: Mimicking the presentation of panic attack.

Psychiatry Res 2020 03 3;285:112720. Epub 2019 Dec 3.

Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217 Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.psychres.2019.112720DOI Listing
March 2020

Prenatal Exposure to Acetaminophen and the Risk of Attention-Deficit/Hyperactivity Disorder: A Nationwide Study in Taiwan.

J Clin Psychiatry 2019 09 10;80(5). Epub 2019 Sep 10.

Department of Psychiatry, No. 201, Shih-Pai Rd, Sec. 2, 11217, Taipei, Taiwan.

Background: Studies have suggested that a significant association exists between prenatal exposure to acetaminophen and the offspring's attention-deficit/hyperactivity disorder (ADHD) risk. However, this association has largely been unexplored among the Asian population, generally, and the Taiwanese population, specifically.

Methods: In our study, 950 study pairs (children with ADHD [ICD-9-CM code: 314] and their mothers) and 3,800 control pairs (children without ADHD and their mothers) matched by demographic characteristics were identified between 1998 and 2008 from the Taiwan Longitudinal Health Insurance Database. Maternal use of acetaminophen was assessed in the first trimester, second trimester, and third trimester of pregnancy and over the period from 3 months before pregnancy to the date of last menstrual cycle.

Results: Logistic regression analysis with adjustments for demographic data, gestational infections, comorbid perinatal conditions, and maternal mental health disorders indicated that exposure to acetaminophen in the second trimester (odds ratio [OR] = 1.19; 95% CI, 1.00-1.40), both the first and second trimesters (OR = 1.28; 95% CI, 1.00-1.64), or in any trimester (OR = 1.20; 95% CI, 1.01-1.42) was associated with an increased risk of ADHD in offspring. Sensitivity analysis excluding gestational infections and maternal mental health disorders confirmed this association (OR = 1.33; 95% CI, 1.04-1.69).

Conclusion: Prenatal exposure to acetaminophen was associated with an increased risk of ADHD in offspring, regardless of gestational infections and maternal mental health disorders. Additional studies are necessary to clarify the underlying mechanisms by which prenatal exposure to acetaminophen leads to neurodevelopmental risks.
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http://dx.doi.org/10.4088/JCP.18m12612DOI Listing
September 2019

Bipolar disorder and risk of Parkinson disease: A nationwide longitudinal study.

Neurology 2019 06 22;92(24):e2735-e2742. Epub 2019 May 22.

From the Departments of Psychiatry (M.-H.H., C.-M.C., K.-L.H., J.-W.H., Y.-M.B., T.-P.S., C.-T.L., S.-J.T., W.-C.L., M.-H.C.) and Family Medicine (T.-J.C.), Taipei Veterans General Hospital; Department of Psychiatry (C.-M.C., K.-L.H., J.-W.H., Y.-M.B., T.-P.S., C.-T.L., S.-J.T., W.-C.L., M.-H.C.), College of Medicine, and Institute of Hospital and Health Care Administration (T.-J.C.), National Yang-Ming University; Department of Psychiatry (T.-P.S.), Cheng Hsin General Hospital, Taipei; and Department of Psychiatry (C.-M.C.), Taipei Veterans General Hospital, Yuanshan Branch, Taiwan.

Objective: To evaluate the risk of Parkinson disease (PD) among patients with bipolar disorder (BD).

Methods: Using the Taiwan National Health Insurance Research Database, we examined 56,340 patients with BD and 225,360 age- and sex-matched controls between 2001 and 2009 and followed them to the end of 2011. Individuals who developed PD during the follow-up period were identified.

Results: Patients with BD had a higher incidence of PD (0.7% vs 0.1%, < 0.001) during the follow-up period than the controls. A Cox regression analysis with adjustments for demographic data and medical comorbid conditions revealed that patients with BD were more likely to develop PD (hazard ratio [HR] 6.78, 95% confidence interval [CI] 5.74-8.02) than the control group. Sensitivity analyses after exclusion of the first year (HR 5.82, 95% CI 4.89-6.93) or first 3 years (HR 4.42; 95% CI 3.63-5.37) of observation showed consistent findings. Moreover, a high frequency of psychiatric admission for manic/mixed and depressive episodes was associated with an increased risk of developing PD.

Conclusion: Patients with BD had a higher incidence of PD during the follow-up period than the control group. Manic/mixed and depressive episodes were associated with an elevated likelihood of developing PD. Further studies are necessary to investigate the underlying pathophysiology between BD and PD.
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http://dx.doi.org/10.1212/WNL.0000000000007649DOI Listing
June 2019

Coaggregation of Major Psychiatric Disorders in First-Degree Relatives of Individuals With Attention-Deficit/Hyperactivity Disorder: A Nationwide Population-Based Study.

J Clin Psychiatry 2019 04 30;80(3). Epub 2019 Apr 30.

Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable mental illness that is easily passed from one generation to the next. Studies have shown that first-degree relatives (FDRs; ie, parents, offspring, and siblings) of individuals with ADHD had a higher risk of also having ADHD. However, the familial coaggregation of ADHD with other major psychiatric disorders, specifically schizophrenia (ICD-9-CM code 295), bipolar disorder (ICD-9-CM cods 296 except codes 296.2, 296.3, 296.9, and 296.82), major depressive disorder (ICD-9-CM codes 296.2 and 296.3), and autism spectrum disorder (ASD; ICD-9-CM code 299), remains unclear.

Methods: Among the entire Taiwanese population in 2010, there were 220,966 parents of children with ADHD (ICD-9-CM code 314), 174,460 siblings of children with ADHD, and 5,875 children of parents with ADHD. Matched control individuals who did not have FDRs with ADHD (1:4) were selected based on age, sex, and their relation to family members.

Results: FDRs (parents, offspring, siblings, and twins) of ADHD-diagnosed individuals had higher relative risks (95% CI) of major psychiatric disorders than the controls: 1.69 (1.60-1.79) for schizophrenia, 2.21 (2.10-2.32) for bipolar disorder, 2.08 (2.02-2.13) for major depressive disorder, 4.14 (3.90-4.39) for ASD, and 6.87 (6.73-7.01) for ADHD.

Discussion: These results show that ADHD coaggregated with other major psychiatric disorders, specifically schizophrenia, bipolar disorder, major depressive disorder, and ASD, within families. The results suggest that public health officials and psychiatrists should closely monitor and follow the mental health of FDRs of ADHD-diagnosed individuals, such as parents and siblings of children with ADHD.
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http://dx.doi.org/10.4088/JCP.18m12371DOI Listing
April 2019
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